P1190: EFFICACY AND SAFETY OF SELINEXOR COMBINING WITH R-CHOP IN THE TREATMENT OF NEWLY DIAGNOSED HIGH RISK (IPI 3-5) GCB SUBTYPE DLBCL PATIENTS: A MULTICENTER RETROSPECTIVE REAL-WORLD STUDY FROM CHINA.
Authors: LI Zhi-Ming, Hang Yang, Yanxue Yin, Yajun LI, Shiyong Zhou, Peng Sun, Yu Wang, Lu Zhang, Hui Zhou, Huilai Zhang
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and highly heterogeneous lymphoma, and for high risk group who has an International Prognostic Index (IPI) score of 3-5 it is more difficult to treat [1, 2]. Under the standard R-CHOP-like immunochemotherapy, the 3-year overall survival (OS) rate of patients with IPI score of 0-1, 2, 3, 4-5 were 91%, 81%, 65% and 59%, respectively[2]. The efficacy for high risk population (IPI 3-5) was limited even after intensive chemotherapy, with an ORR of 74.5% and CR of 47.3% under R-CODOX-M/R-IVAC[3]. Nonetheless, adding new agents to R-CHOP shows better efficacy in patients with IPI 3-5[4, 5]. GCB subtype has better prognosis, but 20% of patients still relapsed after R-CHOP [6], and no more benefit was achieved by modifying regimen with new agent like pola-R-CHP[4]. Selinexor is the only approved oral selective nuclear exportin inhibitor which shown a 34% of ORR in GCB subgroup as a monotherapy in relapsed/refractory DLBCL[7].To provide real world setting data in the patients with IPI score of 3-5 and GCB subtype, we retrospectively analyzed 17 newly diagnosed (ND) high risk (IPI 3-5) GCB subtype DLBCL patients treated with Selinexor and R-CHOP from 4 centers in China. Aims: To evaluate the efficacy and safety of Selinexor+R-CHOP in the treatment of high risk (IPI 3-5) GCB subtype DLBCL patients in real world settings. Methods: 17 ND high risk (IPI 3-5) GCB subtype DLBCL patients from 4 clinical sites treated with Selinexor combined with R-CHOP by January 31, 2023 were included. The objective response, overall survival, and safety data were evaluated. Results: The median age was 60 years (range 30-74, 35%≥65yrs), with 8 males (47.1%). All patients were in advanced stage according to Ann Arbor staging system, with 16 patients in stage IV, and 1 in stage III. All patients were treated with Selinexor and standard R-CHOP except for 1 patient who is old (74 years old) and frail treated with R-miniCHOP+ Selinexor. Selinexor was given 40/60mg (8/9 patients) QW initially. The ORR and CR were 94.1% and 58.8%, respectively. The ORR and CR in 5 patients with double expressor lymphoma (DEL) were 100% and 60%; 2 patients with molecular high grade lymphoma (MHGL) both responded (1CR 1PR); 8 of 13 patients with ≥2 extranodal lesions completely responded (CR 61.5% ORR 92.3%). Median PFS and OS were not reached yet with a median follow-up of 5 months (range 2-14 months). 2 patients got progressed disease in 2 months, and the other 2 progressed after 4 months of treatment. Common treatment-relate adverse events (all grades, grade 3/4) included: neutropenia (63%, 56%), anemia (50%, 25%), thrombocytopenia (50%, 19%), leukopenia (44%, 44%), fatigue (38%,0%), anorexia (31%,0%), hypertriglyceridemia (31%,0%), nausea/vomiting (25%,6%). All AEs can be managed with appropriate supportive care and dose adjustments. 6 out of 9 patients got dose reduction of Selinexor to 40mg (initial in 60mg QW) due to AE, with 1 happened in C2 and the other 5 happened in C4-C5. All patients were continuously treated after dose reduction, and no treatment-related death occurred. Overall, 10 patients finished 6 cycles of Selinexor+R-CHOP treatment, 3 patients were still receiving therapy. Summary/Conclusion: Once weekly Selinexor can be safely combined with R-CHOP in ND high risk (IPI 3-5) GCB subtype DLBCL patients with ORR≥94% and CR of 59%. These data support further investigation in prospective randomized studies in high-risk GCB subtype population.Keywords: Germinal center, International prognostic index, DLBCL, High risk